The natural history of chronic HCV infection is very variable and retrospective studies have identified both slow progressors who take 40 years to develop cirrhosis and rapid progressors who may develop advanced fibrosis in as little as 10 - 20 years. The underlying pathophysiological mechanisms associated with disease progression are poorly understood and represent the central focus of this HCV Center. We will study cohorts of patients with variable rates of disease progression. The Clinical Center for HCV disease progression will provide liver tissues, specimens, clinical expertise, biostatistics and a pathology core to interact with the basic Investigators in this HCV Center proposal. The clinical center will utilize both existing cohorts and develop novel cohorts of patients with either slow or fast disease progression to study the underlying immunological, virological and metabolic factors associated with progression of liver fibrosis. In particular we will develop: 1) the Infrastructure for clinical investigation into mechanisms of disease progression and fibrosis in patients with HCV 2) Evaluation of 4 distinct cohorts of patients who have variable rates of fibrosis progression: A) Patients with HCV naive to treatment representing a control group of predominantly slow progressors B) Patients with HCV and Schistosomiasis who rapidly develop cirrhosis C) Patients with HIV/HCV;a subset of whom are immunocompromised with low CD4 counts and may progress more rapidly D) Patients post liver transplant who have recurrent HCV These studies may help identify the mechanism of fibrosis progression and lead to rational use of reources to identify and treat patients at higher risk of disease progression.